Isoxazolyl indolamines having anti-diabetic activity

Abstract

This disclosure describes novel compounds of the formula <IMAGE> where m is 2, 3 or 4 X is hydrogen or hydroxy R1 represents hydrogen, fluoro, chloro, lower alkyl having 1 to 4 carbon atoms or lower alkoxy having 1 to 4 carbon atoms, and R2 and R3 each independently represent lower alkyl as defined above, or R2 and R3 together with N represent <IMAGE> wherein n is 1, 2 or 3, and R4 represents hydrogen or lower alkyl as defined above, and R5 represents hydrogen, lower alkyl, phenyl or phenyl substituted with fluoro, chloro, lower alkyl having 1 to 4 carbon atoms, or lower alkoxy having 1 to 4 carbon atoms, with the proviso that when X is hydroxy, m is 3 or 4, or a pharmaceutically acceptable acid addition salt thereof, which are useful in the treatment of diabetes by inhibiting or impeding post-prandial hyperglycemia.

What is claimed is: 
     
       1. A compound of the formula ##STR17## where m is 2, 3, or 4, X is hydrogen or hydroxy,   R 1  represents hydrogen, fluoro, chloro, lower alkyl having 1 to 4 carbon atoms, or lower alkoxy having 1 to 4 carbon atoms, and   R 2  and R 3  each independently represent lower alkyl having 1 to 4 carbon atoms, or   R 2  and R 3  together with N represent ##STR18## wherein n is 1, 2 or 3, and   R 4  represents hydrogen or lower alkyl having 1 to 4 carbon atoms, and   R 5  represents hydrogen, lower alkyl, phenyl or phenyl substituted with fluoro, chloro, lower alkyl having 1 to 4 carbon atoms or lower alkoxy having 1 to 4 carbon atoms with the proviso that when X is hydroxy, m is 3 or 4, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       2. A compound of the formula ##STR19## wherein R 1  represents hydrogen, fluoro, chloro, lower alkyl having 1 to 4 carbon atoms, or lower alkoxy having 1 to 4 carbon atoms, and R 2  and R 3  each independently represent lower alkyl having 1 to 4 carbon atoms, or   R 2  and R 3  together with N represent ##STR20## wherein n is 1, 2 or 3, and   R 4  represents hydrogen or lower alkyl having 1 to 4 carbon atoms, and   R 5  represents hydrogen, lower alkyl or unsubstituted phenyl or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       3. A compound of the formula ##STR21## wherein R 1 , R 2 , R 3  and R 5  are as defined in claim 2 or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       4. The compound of claim 2 wherein R 5  is ethyl. 
     
     
       5. The compound of claim 2 wherein R 5  is unsubstituted phenyl. 
     
     
       6. The compound of claim 2 which is 2-(5-methyl-3-phenyl-4-isoxazolyl)-3-(3-dimethylaminopropyl)-indole or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       7. The compound of claim 2 which is 2-(3-ethyl-5-methyl-4-isoxazolyl)-3-(3-dimethylaminopropyl)-indole or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       8. The compound of claim 2 which is 2-(5-methyl-3-phenyl-4-isoxazolyl)-3-(3-pyrrolidinopropyl)-indole or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       9. The compound of claim 1 which is 2-(3-ethyl-5-methyl-4-isoxazolyl)-3-(4-dimethylaminobutyl)-indole or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       10. A compound of the formula ##STR22## wherein R 1 , R 2 , R 3 , R 4  and R 5  are as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       11. A compound of the formula ##STR23## where R 5  is phenyl, and R 1 , R 2 , R 3  and R 4  are as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       12. A compound of the formula ##STR24## where R 1 , R 4  and R 5  are as defined in claim 1. 
     
     
       13. A method of treating diabetes by inhibiting post-prandial hyperglycemia which comprises administering to an animal in need of said treatment an effective amount of a compound of claim 1. 
     
     
       14. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable diluent or carrier therefor. 
     
     
       15. A method for treating diabetes which comprises administering to an animal in need of said treatment a hypoglycemic effective amount of a compound of claim 1. 
     
     
       16. The compounds of claim 1 in which m is 3 or 4, X is hydrogen or hydroxy and R 1 , R 2 , R 3 , R 4  and R 5  are as defined in claim 1. 
     
     
       17. The compound of claim 10 which is N,N-dimethyl-2-(5-methyl-3-phenyl-4-isoxazolyl)-3-indole-propionamide. 
     
     
       18. The compound of claim 10 which is N-N-dimethyl-2-(3-ethyl-5-methyl-4-isoxazolyl)-3-indole-propionamide. 
     
     
       19. The compound of claim 12, which is 2-(5-methyl-3-phenyl-4-isoxazolyl)-3-indole propionic acid. 
     
     
       20. The compound of claim 12, which is 2-(3-ethyl-5-methyl-4-isoxazolyl)-3-indole propionic acid.